The invention concerns the economical production or preparation of reagent carriers for the qualitative or quantitative determination of analytes in liquids and in particular in body fluids. Such known reagent carriers are able to bind analyte molecules from the sample liquid on a carrier surface in a reaction (“assay”) where the binding events can be detected by measurement techniques e.g. by the optical detection of fluorescence events. Reagent carriers of this type can for example be prepared with microarray structures by the process of the present invention in order to for example produce a biochip for the selective local detection of binding reactions.
However, the invention is not limited to the production of biochips with microarrays but is also suitable for producing two-dimensionally coated carriers such as microtitre plates or microtitre strips.
In the production of reagent carriers of the type considered here, an individual surface area of the previously prepared reagent carrier body is contacted with a liquid or liquids in a well defined time sequence. Preparation devices are used for this which have technical equipment for the volume-controlled addition of liquids. Furthermore, preparation devices may be used which have equipment to remove previously added liquids or to remove weakly bound or entrapped molecules or particles from the surface of the carrier body. Moreover, washing devices, drying devices etc. may also be used as treatment devices.
The preparation devices usually include a control device for controlling predetermined time sequences of process steps. The sequence of the process steps can be interrupted by waiting times that are necessary to allow the reactions to run. For this purpose the reagent carrier bodies can be transported to interim storage positions in the preparation device or outside the preparation device. The interim storage positions may be equipped with temperature control devices, shakers etc. for the reagent carrier bodies.
In conventional systems for producing or preparing reagent carriers, a particular reagent carrier body is transported to a treatment device and is subjected there in a resting state to a treatment step. After treatment the reagent carrier body is then removed from the treatment zone and optionally conveyed to another treatment device. This conventional procedure generally only allows a relatively low output of prepared reagent carriers per time unit. Proposals have already been made to run several treatment devices in parallel in one preparation device. These treatment devices are provided in a multiple design such that they can treat groups of reagent carrier bodies in parallel. Although this enables a higher throughput in the preparation of reagent carriers, the problem arises that different results occur in the treatment of the individual reagent carrier bodies due to variability among the individual treatment devices. Hence more effort is required to ensure an adequately identical functionality among the parallel treatment channels and to verify this by testing.
In some cases it is not practical to run preparation steps on several reagent carrier bodies in parallel. An example of this is the precisely positioned deposition of drops of liquid in the production of microarrays. In this case the aim is to apply different liquids to different areas of the surface of a reagent carrier body in order to be able to simultaneously determine several different components of the sample liquid in a later assay within the same run because the different areas undergo different specific reactions with components of the sample liquid. A high throughput system with outputs of up to 5000 carriers per day is described in the publication “Kuhn et al., BIOforum Int., p. 30 ff, 2000-1”.
It is also already known in the case of test strip manufacture that the carrier paper can be reeled off a storage roll and that the strip tape is passed through an immersion bath or sprayed with test substances in a continuous process. However, the coating process is followed by a very laborious process of device manufacture in which the strip tape is cut into shape and the separate paper strips are laboriously fitted into individual holders and assembled to form manageable elements.